Transcript 451_07_daggett_Lect9..

Hepatitis B
• Epidemic jaundice described by
Hippocrates in 5th century BC
• Jaundice reported among recipients
of human serum and yellow fever
vaccines in 1930s and 1940s
• Australia antigen described in 1965
• Serologic tests developed in 1970s
Hepatitis B Virus
• Hepadnaviridae family (DNA)
• Numerous antigenic components
• Humans are only known host
• May retain infectivity for more
than 7 days at room temperature
Hepatitis B Virus Infection
• More than 350 million chronically
infected worldwide
• Established cause of chronic
hepatitis and cirrhosis
• Human carcinogen—cause of up
to 80% of hepatocellular
carcinomas
Hepatitis B Virus
HBsAg
HBcAg
HBeAg
Hepatitis B Clinical Features
• Incubation period 60-150 days
(average 90 days)
• Nonspecific prodrome of malaise,
fever, headache, myalgia
• Illness not specific for hepatitis B
• At least 50% of infections
asymptomatic
Hepatitis B Complications
• Fulminant hepatitis
• Hospitalization
• Cirrhosis
• Hepatocellular carcinoma
• Death
Chronic Hepatitis B
Virus Infection
• Chronic viremia
• Responsible for most mortality
• Overall risk 5%
• Higher risk with early infection
Risk of Chronic HBV Carriage
by Age of Infection
100
Carrier risk (%)
90
80
70
60
50
40
30
20
10
0
Birth
1-6 mo
7-12 mo
Age of infection
1-4 yrs
5+ yrs
Hepatitis B Epidemiology
• Reservoir
Human
• Transmission
Bloodborne
Subclinical
cases
transmit
• Communicability
1-2 months before
and after onset of
symptoms
Chronic
Hepatitis B Perinatal
Transmission*
• If mother positive for HBsAg and HBeAg
–70%-90% of infants infected
–90% of infected infants become
chronically infected
• If positive for HBsAg only
–5%-20% of infants infected
–90% of infected infants become
chronically infected
*in the absence of postexposure prophylaxis
Hepatitis B—United States, 1978-2005
Decline among
men who have sex with men
30000
Decline among
IV drug users
25000
Cases
20000
15000
10000
Hepatitis B vaccine licensed
5000
0
1978 1980
1985
1990
Year
1995
2000
2005
HBV Disease Burden in the
United States*
New infections
78,000/yr
Current carriers
>1 million
New carriers
>5,000/yr
Death
5,000/yr
*2001 estimates
Risk Factors for Hepatitis B
Unknown
16%
Other
5%
Heterosexual,
multiple
partners
39%
IV drug users
IDU
16%
Gay men
MSM
24%
MMWR 2006;55(RR-16):6-7
Hepatitis B Virus Infection by
Duration of High-Risk Behavior
IV drug user
HCWs
Homosexual men
Heterosexual
Percent infected
100
80
60
40
20
0
0
3
6
9
Years at Risk
12
15
Strategy to Eliminate Hepatitis B
Virus Transmission—United States
• Prevent perinatal HBV
transmission
• Routine vaccination of all infants
• Vaccination of adults in high-risk
groups
Prevention of Perinatal
Hepatitis B Virus Infection
• Begin treatment within 12 hours
of birth
• Hepatitis B vaccine (first dose)
and HBIG at different sites
• Complete vaccination series at 6
months of age
• Test for response at 9-18 months
of age
Hepatitis B Vaccine
• Composition
Recombinant HBsAg
• Efficacy
95% (Range, 80%-100%)
• Duration of
Immunity
• Schedule
>20 years
3 Doses
• Booster doses not routinely recommended
Hepatitis B Vaccine
Routine Infant Schedule
Minimum
Interval
Dose+
Usual Age
Primary 1
Primary 2
Primary 3
Birth
--1- 2 months 4 weeks
6-18 months* 8 weeks**
* infants who mothers are HBsAg+ or whose HBsAg status is
unknown should receive the third dose at 6 months of age
** at least 16 weeks after the first dose
+an additional dose at 4 months is acceptable if the clinician prefers to
use a combination vaccine that contains hepatitis B vaccine
Protection* by Age Group and Dose
Dose
Infants**
Teens and Adults***
1
16%-40%
20%-30%
2
80%-95%
75%-80%
3
98%-100%
90%-95%
* Anti-HBs antibody titer of 10 mIU/mL or higher
** Preterm infants less than 2 kg have been shown to
respond to vaccination less often
*** Factors that may lower vaccine response rates are age
>40 years, male gender, smoking, obesity, and immune
deficiency
Postvaccination Serologic Testing
• Not routinely recommended
•
following vaccination of infants,
children, adolescents, or most adults
Recommended for:
–chronic hemodialysis patients
–other immunocompromised persons
–persons with HIV infection
–sex partners of HBsAg+ person
–infants born to HBsAg+ women
–certain healthcare workers
Postvaccination Serologic Testing
Healthcare workers who have
contact with patients or blood
should be tested for antibody
after vaccination
Hepatitis B Vaccine
Adverse Reactions
Pain at injection site
Infants and
Adults
Children
13%-29%
3%-9%
11%-17%
0%-20%
Temperature ≤99.9°F (37.7°C)
1%
0.4%-6%
Severe systemic reactions
rare
rare
Mild systemic complaints
(fatigue, headache)